Dioclein, a new nitric oxide- and endothelium-dependent vasodilator flavonoid

In the present work, the vasorelaxant effect of dioclein, a new flavonoid i solated from Dioclea grandiflora (Leguminoseae), was investigated in the ra t aorta. Dioclein induced a concentration-dependent relaxation in vessels p re-contracted with phenylephrine (IC50 = 1.3 +/- 0.3 mu M), a response whic h was abolished after endothelium removal. Neither indomethacin (10 mu M), an inhibitor of cyclo-oxygenase, nor atropine (1 mu M), an antagonist of mu scarinic receptors, modified the effect of dioclein. Dioclein (30 mu M) ind uced a significant increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in aortic rings with endothelium. The nitric oxide (NO) syntha se inhibitor, N-G-nitro-L-arginine-methyl-ester (L-NAME, 300 mu M), strongl y inhibited or abolished the relaxing effect and rise in cyclic GMP levels induced by dioclein. Furthermore, dioclein (30 mu M) had no effect on the e ndothelium-independent relaxation produced by the NO donor, 3-morpholino-sy dnonimine (SIN-1), while superoxide dismutase (100 U ml(-1)) significantly potentiated it. These results indicate that, in the rat aorta, dioclein ind uces a NO- and endothelium-dependent vasorelaxant effect, which is associat ed with cyclic GMP elevation. This vasorelaxation likely results from enhan ced synthesis of NO rather than enhanced biological activity of NO. (C) 199 9 Elsevier Science B.V. All rights reserved.